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SRP169118
Danio rerio
24 Downloadable Samples
Illumina HiSeq 2500
Description
Glucocorticoid drugs are widely used to treat immune-related diseases, but their use is limited by side effects and by resistance, which especially occurs in macrophage-dominated diseases. In order to improve glucocorticoid therapies, more research is required into the mechanisms of glucocorticoid action. In the present study, we have used a zebrafish model for inflammation to study glucocorticoid effects on the innate immune response. In zebrafish larvae, the migration of neutrophils towards a site of injury is inhibited by the synthetic glucocorticoid beclomethasone, while migration of macrophages is glucocorticoid resistant. RNA sequencing was done on on Fluorescence-Activated Cell Sorting (FACS)-sorted macrophages.The results show that the vast majority of the wounding-induced transcriptional changes in these cells are inhibited by beclomethasone, whereas a small subset is glucocorticoid-insensitive. As a result, beclomethasone decreases the number of macrophages that differentiate towards a pro-inflammatory (M1) phenotype, which we demonstrated using a tnfa:eGFP-F reporter line and analysis of macrophage morphology. We conclude that the glucocorticoid resistance of the wounding-induced macrophage migration is due to the insensitivity of the induction of macrophage-specific chemoattractants to glucocorticoid inhibition, which may explain the relative resistance of macrophage-dominated diseases to glucocorticoid therapy. However, the induction of pro-inflammatory genes in macrophages is strongly attenuated, which inhibits their differentiation to an M1 phenotype. Overall design: After anesthesia with 0.02% aminobenzoic acid ethyl ester (tricaine, Sigma Aldrich), the tails of 3 days post fertilization (dpf) embryos were partially amputated with a 1mm sapphire blade (World Precision Instruments) on 2% agarose-coated Petri dishes under a Leica M165C stereomicroscope (Chatzopoulou et al., 2016). Amputated and non-amputated (control) embryos were pretreated for 2 hours with 25 µM beclomethasone (Sigma Aldrich) or vehicle (0.05% dimethyl sulfoxide (DMSO)) in egg water prior to amputation and received the same treatment after the amputation. Macrophages were sorted from Tg(mpeg1.4:mCherry-F) embryos as previously described (Rougeot et al., 2014; Zakrzewska et al., 2010) at 4 hours post amputation (hpa). The sorted cells were collected in QIAzol lysis reagent (Qiagen) for RNA isolation. Extracted total RNA was amplified using the SMART-seq V4 kit (Clontech) for sequencing. The RNA seq libraries generated with the SMART-seq V4 kit were sequenced using an Illumina HiSeq 2500 instrument according to the manufacturer's instructions with a read length of 50 nucleotides.
Publication Title
Glucocorticoids inhibit macrophage differentiation towards a pro-inflammatory phenotype upon wounding without affecting their migration.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
In order to identify genes dysregulated by the aberrant transcriptional activity of RUNX1-RUNX1T1, we used microarrays to determine the effect of this mutation on gene expression during myeloid and erythroid development of normal human progenitor cells.
Publication Title
Transcriptional dysregulation mediated by RUNX1-RUNX1T1 in normal human progenitor cells and in acute myeloid leukaemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the deregulation of expression in E9.5 male mouse embryos are that homozygous for a mutant allele of the Smchd1 gene (ie Smchd1MommeD1/MommeD1). Overall design: RNA-seq analysis of Smchd1+/+ vs Smchd1MommeD1/MommeD1
Publication Title
Smchd1 regulates a subset of autosomal genes subject to monoallelic expression in addition to being critical for X inactivation.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cross-species gene expression analysis identifies a novel set of genes implicated in human insulin sensitivity.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent discovery reveals HFD insult can cause insulin resistance very rapidly, but the underlying mechanism is still not well understood. We performed a short term experiment in a Diet Induced Insulin resistance mouse model.
Publication Title
Cross-species gene expression analysis identifies a novel set of genes implicated in human insulin sensitivity.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 4000
Description
Gata2, a zinc finger TF, is essential for the generation and survival of HSCs in the embryo and has been implicated in the pathogenesis of AML, yet the requirement for Gata2 in adult HSCs and LSCs remains unclear. Using a conditional mouse model where Gata2 was deleted specifically in hematopoietic cells, we show that knockout of Gata2 leads to a rapid and complete cell-autonomous loss of adult HSCs. In Meis1a/Hoxa9 driven AML, deletion of Gata2 impedes maintenance and self-renewal of LSCs. We then performed RNA-seq from sorted control and Gata2 KO LSCs (CD45.2+ c-Kit+) after pIpC treatment in transplanted mice. Overall design: Wild Type and Gata2-/- Meis1a/Hoxa9 LSCs were harvested from mice 24 days after pIpC administration
Publication Title
Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 4000
Description
Gata2, a zinc finger TF, is essential for the generation and survival of HSCs in the embryo and has been implicated in the pathogenesis of AML, yet the requirement for Gata2 in adult HSCs and LSCs remains unclear. Using a conditional mouse model where Gata2 was deleted specifically in hematopoietic cells, we show that knockout of Gata2 leads to a rapid and complete cell-autonomous loss of adult HSCs. We then performed RNA-seq in sorted HSCs (LSK CD48- CD150+) from control and Gata2+/fl;Vav-iCre+ 8-to-10-week old mice. Overall design: Wild Type and Gata2+/- HSCs were harvested from 8-to-10-week old mice
Publication Title
Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia.
Sample Metadata Fields
Cell line, Subject
View Samples- Plasmodium falciparum
- 9 Downloadable Samples
- Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
Transient regulation of Plasmodium numbers below the density that induces fever has been observed in chronic malaria infections in humans and this species transcending control cannot be explained by immunity alone. Using an in vitro system we have observed density dependent regulation of malaria parasitemia as a mechanism to possibly explain these in vivo observations.
Publication Title
A high parasite density environment induces transcriptional changes and cell death in Plasmodium falciparum blood stages.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2000
Description
Toxoplasma gondii is an obligate intracellular Apicomplexan parasite capable of invading and surviving within nucleated cells in most warm-blooded animals. This remarkable task is achieved through the delivery of effector proteins from the parasite into the parasitophorous vacuole and host cell cytosol that rewire host cellular pathways, facilitating parasite evasion of the immune system. Here, we have identified a novel export pathway in Toxoplasma that involves cleavage of effector proteins by the Golgi-resident aspartyl protease 5 (ASP5) prior to translocation into the host cell. We demonstrate that ASP5 cleaves a highly constrained amino acid motif that has some similarity to the PEXEL motif of Plasmodium parasites. We show that ASP5 can mature effectors at both the N- and C-terminal ends of proteins and is also required for the trafficking of proteins without this motif. Furthermore, we show that ASP5 controls establishment of the nanotubular network and is required for the efficient recruitment of host mitochondria to the parasitophorous vacuole membrane. Global assessment of host gene expression following infection reveals that ASP5-dependent pathways influence thousands of the transcriptional changes that Toxoplasma imparts on its host cell. This work characterizes the first identified machinery required for export of Toxoplasma effectors into the infected host cell. Overall design: Three groups of human foreskin fibroblasts are compared. Each group has 3 replicates giving a total of 9 samples. The first group of samples are infected with wild type (GRA16HA) Toxoplasma gondii, the second group with Asp5 knock-out Toxoplasma gondii, and the final group remain uninfected. All fibroblasts are generated from one donor sample.
Publication Title
An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of MCF-7 cells treated for 4h with Ethanol, Estradiol (E2), Dexamethasone (Dex), or Estradiol + Dexamethasone (E2 + Dex)
Publication Title
GR and ER Coactivation Alters the Expression of Differentiation Genes and Associates with Improved ER+ Breast Cancer Outcome.
Sample Metadata Fields
Cell line
View Samples